BACKGROUND:Steroid-induced osteonecrosis of the femoral head(SANFH)is a severe orthopedic disease characterized by interruption of the blood supply to the femoral head and necrosis of subchondral bone,leading to joint dysfunction.Long-term use of glucocorticoids is the main cause of SANFH,and its pathogenesis involves multiple factors,including intravascular coagulation and osteocyte apoptosis.Vascular endothelial growth factor A(VEGF-A),as a key angiogenic factor,has potential value in the treatment of SANFH.OBJECTIVE:To summarize the mechanisms of action of VEGF-A in SANFH,including its progress in promoting angiogenesis,anti-apoptosis,and lipid metabolism regulation,and to discuss the prospects for clinical application of VEGF-A targeted therapy.METHODS:Literature related to VEGF-A targeted regulation of angiogenesis in the treatment of SANFH was identified through searches of PubMed,Web of Science,CNKI,and WanFang databases from database inception to November 2024.After quality assessment,71 articles were selected,data were extracted by independent researchers,and disagreements were resolved through group discussions.RESULTS AND CONCLUSION:(1)VEGF-A binds to its receptors VEGFR-1 and VEGFR-2,activating downstream signaling pathways that promote the proliferation,migration,and angiogenesis of endothelial cells.Therefore,it can promote the formation of collateral circulation and improve blood supply to the area of bone necrosis.(2)Reduced expression of VEGF-A may lead to a decrease in the number of blood vessels within bone tissue,exacerbating the ischemic state of the femoral head.Furthermore,VEGF-A has anti-apoptotic effects and reduce apoptosis in osteocytes and bone marrow cells,thus protecting bone tissue.(3)The role of VEGF-A in regulating lipid metabolism and inflammatory responses,as well as promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,provides a new perspective for the treatment of SANFH.(4)The development of VEGF-A protein delivery systems,such as lipid nanoparticles and exosome-based delivery systems,offers new possibilities for the clinical application of VEGF-A.(5)The research progress of VEGF-A in SANFH treatment has laid a solid foundation for the development of new treatment strategies and has opened up new avenues for future research directions and clinical applications.(6)With further clarification of the mechanisms of action of VEGF-A and continuous advancements in delivery technologies,more effective treatments will be provided for SANFH patients,improving their prognosis.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is complex,involving vascular endothelial injury,osteocyte apoptosis,inflammatory responses,and bone metabolism disorders.MicroRNAs(miRNAs),as key regulators of gene expression,play an important role in steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To comprehensively analyze the regulatory role of miRNAs in steroid-induced osteonecrosis of the femoral head and to evaluate their potential as biomarkers and therapeutic tools.METHODS:Relevant literature was retrieved from PubMed,Web of Science,CNKI,and WanFang databases using specific keywords,and articles were selected based on the inclusion and exclusion criteria.By reading titles,abstracts,or full texts,articles with poor relevance or repetitive content were excluded,and 76 articles were finally included for analysis.RESULTS AND CONCLUSION:miRNAs regulate gene expression by binding to the 3'untranslated region of target mRNAs,affecting cell differentiation,proliferation,apoptosis,and stress responses.Specific miRNAs such as miR-33-5p,miR-99a,miR-106b-5p,miR-155,miR-146a,and miR-21 play a central regulatory role in vascular injury,inflammatory responses,osteocyte differentiation,and apoptosis in steroid-induced osteonecrosis of the femoral head.Additionally,the expression patterns of miRNAs are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head,showing potential as biomarkers.Although miRNAs shows great potential as biomarkers in therapeutic strategies,the current limitation of sample size and lack of multi-population validation restrict the universality and reliability of the results.Moreover,the efficacy and safety of miRNA therapeutic strategies(including off-target effects and delivery issues)remain major challenges in realizing clinical applications.

BACKGROUND:Steroid-induced osteonecrosis of the femoral head(SANFH)is a severe orthopedic disease characterized by interruption of the blood supply to the femoral head and necrosis of subchondral bone,leading to joint dysfunction.Long-term use of glucocorticoids is the main cause of SANFH,and its pathogenesis involves multiple factors,including intravascular coagulation and osteocyte apoptosis.Vascular endothelial growth factor A(VEGF-A),as a key angiogenic factor,has potential value in the treatment of SANFH.OBJECTIVE:To summarize the mechanisms of action of VEGF-A in SANFH,including its progress in promoting angiogenesis,anti-apoptosis,and lipid metabolism regulation,and to discuss the prospects for clinical application of VEGF-A targeted therapy.METHODS:Literature related to VEGF-A targeted regulation of angiogenesis in the treatment of SANFH was identified through searches of PubMed,Web of Science,CNKI,and WanFang databases from database inception to November 2024.After quality assessment,71 articles were selected,data were extracted by independent researchers,and disagreements were resolved through group discussions.RESULTS AND CONCLUSION:(1)VEGF-A binds to its receptors VEGFR-1 and VEGFR-2,activating downstream signaling pathways that promote the proliferation,migration,and angiogenesis of endothelial cells.Therefore,it can promote the formation of collateral circulation and improve blood supply to the area of bone necrosis.(2)Reduced expression of VEGF-A may lead to a decrease in the number of blood vessels within bone tissue,exacerbating the ischemic state of the femoral head.Furthermore,VEGF-A has anti-apoptotic effects and reduce apoptosis in osteocytes and bone marrow cells,thus protecting bone tissue.(3)The role of VEGF-A in regulating lipid metabolism and inflammatory responses,as well as promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,provides a new perspective for the treatment of SANFH.(4)The development of VEGF-A protein delivery systems,such as lipid nanoparticles and exosome-based delivery systems,offers new possibilities for the clinical application of VEGF-A.(5)The research progress of VEGF-A in SANFH treatment has laid a solid foundation for the development of new treatment strategies and has opened up new avenues for future research directions and clinical applications.(6)With further clarification of the mechanisms of action of VEGF-A and continuous advancements in delivery technologies,more effective treatments will be provided for SANFH patients,improving their prognosis.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is complex,involving vascular endothelial injury,osteocyte apoptosis,inflammatory responses,and bone metabolism disorders.MicroRNAs(miRNAs),as key regulators of gene expression,play an important role in steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To comprehensively analyze the regulatory role of miRNAs in steroid-induced osteonecrosis of the femoral head and to evaluate their potential as biomarkers and therapeutic tools.METHODS:Relevant literature was retrieved from PubMed,Web of Science,CNKI,and WanFang databases using specific keywords,and articles were selected based on the inclusion and exclusion criteria.By reading titles,abstracts,or full texts,articles with poor relevance or repetitive content were excluded,and 76 articles were finally included for analysis.RESULTS AND CONCLUSION:miRNAs regulate gene expression by binding to the 3'untranslated region of target mRNAs,affecting cell differentiation,proliferation,apoptosis,and stress responses.Specific miRNAs such as miR-33-5p,miR-99a,miR-106b-5p,miR-155,miR-146a,and miR-21 play a central regulatory role in vascular injury,inflammatory responses,osteocyte differentiation,and apoptosis in steroid-induced osteonecrosis of the femoral head.Additionally,the expression patterns of miRNAs are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head,showing potential as biomarkers.Although miRNAs shows great potential as biomarkers in therapeutic strategies,the current limitation of sample size and lack of multi-population validation restrict the universality and reliability of the results.Moreover,the efficacy and safety of miRNA therapeutic strategies(including off-target effects and delivery issues)remain major challenges in realizing clinical applications.

Functional neuroendocrine neoplasm, which secrete hormones and lead to diverse clinical symptoms, pose significant challenges in diagnosis and treatment. Early identification and standardized management are crucial for improving patient prognosis. This article summarized three clinically relatively common cases of Functional pancreatic neuroendocrine neoplasm (F-pNENs), focusing on analyzing their diagnostic key points and standardized therapeutic pathways. It aimed to provide reference for early clinical identification of rare tumors and improvement of standardized multidisciplinary diagnosis and treatment as well as personalized treatment strategies.

Objective:To quantify the effects of different touchdown methods on the knee joint during barefoot running us-ing a validated finite element model of the knee joint,providing a theoretical basis for reducing sports injuries in runners.Method:Kinematics and ground reaction force data were collected from 22 participants during forefoot land-ing,midfoot landing and hindfoot landing at 4 m/s±5％respectively.Knee joint reaction forces were calculated using Visal3D inverse dynamics.The numerical simulations were performed for each of the three ground con-tact processes based on a 3D finite element model of the knee joint.Result:There were significant kinematic differences in the knee joint during forefoot/midfoot touchdown mode and hindfoot touchdown,with a larger peak flexion when using midfoot touchdown.Compared to forefoot touchdown,the midfoot touchdown mode during barefoot running produced a smaller peak in vertical ground reaction force.At the peak vertical ground reaction force,the peak patellofemoral cartilage contact stress(4.83 MPa)and the peak meniscal contact stress(5.98 MPa)in the midfoot touchdown mode were the lowest com-pared to the other two touchdown modes.Conclusion:When running barefoot,using a midfoot landing may reduce the risk of knee injury.It is recom-mended to use the midfoot touch pattern for rehabilitation involving barefoot running.

Objective:To quantify the effects of different touchdown methods on the knee joint during barefoot running us-ing a validated finite element model of the knee joint,providing a theoretical basis for reducing sports injuries in runners.Method:Kinematics and ground reaction force data were collected from 22 participants during forefoot land-ing,midfoot landing and hindfoot landing at 4 m/s±5％respectively.Knee joint reaction forces were calculated using Visal3D inverse dynamics.The numerical simulations were performed for each of the three ground con-tact processes based on a 3D finite element model of the knee joint.Result:There were significant kinematic differences in the knee joint during forefoot/midfoot touchdown mode and hindfoot touchdown,with a larger peak flexion when using midfoot touchdown.Compared to forefoot touchdown,the midfoot touchdown mode during barefoot running produced a smaller peak in vertical ground reaction force.At the peak vertical ground reaction force,the peak patellofemoral cartilage contact stress(4.83 MPa)and the peak meniscal contact stress(5.98 MPa)in the midfoot touchdown mode were the lowest com-pared to the other two touchdown modes.Conclusion:When running barefoot,using a midfoot landing may reduce the risk of knee injury.It is recom-mended to use the midfoot touch pattern for rehabilitation involving barefoot running.

OBJECTIVE To design and synthesize of a series of novel azachalcone derivatives and study of their anti-cervical cancer activity and mechanism of action. METHODS A series of novel chalcone derivatives were designed and synthesized by using glycyrrhiza chalcone as the lead compound and VEGFR-2 and P-gp as the target sites using the active substructure splicing principle, and the structures were characterized by 1H-NMR, 13C-NMR and HR-MS. MTT, ELISA, co-dosing with cisplatin, Western blotting and molecular docking assays were used to preliminarily evaluate the proliferation inhibitory activity and mechanism of action of the target compounds on cervical cancer and cisplatin-resistant cervical cancer cells. RESULTS Compound 7h showed some antitumor activity and reversal of cisplatin resistance, and had some inhibitory effects on phosphorylation of VEGFR-2 and downstream PI3K/AKT signaling pathway proteins, with no significant differences on P-gp protein expression compared with the blank group in the concentration range of 0.5, 1.0, 1.5 μmol·L−1. CONCLUSION The anti-cervical cancer activity and reversal of cisplatin resistance of compound 7h may be related to its inhibition of VEGFR-2 and P-gp targets.

Chalcones are polyphenolic flavonoid substances with various pharmacological effects and low toxicity.In this study, 15 novel trifluoromethyl chalcone derivatives (3a-3o) were designed and synthesized using the chalcone nucleus of natural licorice chalcone as the lead compound skeleton in order to find the candidate drugs with high efficiency and low toxicity against cervical cancer.The structures of the target compounds were confirmed by 1H NMR, 13C NMR and HRMS. The inhibitory activities of compounds 3a-3o, licorice chalcone, cisplatin and Nutlin3a on SiHa, HeLa and C-33A human cervical cancer cells and H8 and HaCaT normal cells were determined by MTT assay, and the structure-activity relationship was analyzed.Transwell and flow cytometry methods were used to assess the target compounds'' ability to inhibit cell migration and invasion, promote apoptosis, and arrest the cell cycle.Molecular docking technology was used to further study the binding characteristics of the target compound with MDM2 protein.The results showed that the compounds had different degrees of inhibitory activity against the three types of cervical cancer cells.Compound 3n showed the strongest activity against HeLa cells (IC50 = 11.69 μmol/L), which was superior to the lead compound, and had lower toxicity against the two normal cells.Compound 3n was found to significantly inhibit the migration and invasion of HeLa cells, induce apoptosis and arrest the cell cycle at G2/M phase.The results of molecular docking showed that the effective binding of compound 3n to MDM2 protein may be one of its anti-tumor mechanisms.This study provides an experimental basis for the screening of new anti-cervical cancer candidate drug from chalcone derivatives.

Objective To observe the clinical effect of benzene sulfonic amlodipine combined with traditional Chinese medicine (TCM) Yangxueqingnao granules for treatment of patients with hypertensive urgencies (HU) with acute headache, and its effect on serum brain derived neurotrophic factor (BDNF) level.Methods A prospective study was conducted, 186 HU patients with acute headache admitted to the Department of Cardiology in the Affiliated Hospital of Southwest University from January 2014 to December 2016 were enrolled, and they were divided into a control group (90 cases) and an observation group (96 cases) by random number table method. The patients in control group received benzene sulfonic amlodipine (10 mg, once a day) and the patients in observation group were additionally given Yangxueqingnao granules (4 g, 3 times a day for consecutive 7 days) on the basis of treatment in control group. The mean arterial pressure (MAP), the nature and location of headache and the levels of serum BNDF were examined before and after treatment and compared between them in the two groups, the degree of headache was evaluated by visual analogue scale (VAS), and the clinical therapeutic effects in the two groups were observed.Results There were no statistical significant differences in MAP (mmHg, 1 mmHg = 0.133 kPa) between the two groups before treatment and at 2 hours, on 1, 3, 7 days after treatment (control group: 99.7±9.5, 94.2±9.1, 88.6±7.6, 81.8±9.3, 75.6±5.3 respectively, the observation group: 95.4±13.5, 91.2±8.1. 88.9±8.7, 83.2±8.6, 77.2±4.8 respectively, allP > 0.05). Compared with the control group, after treatment for 1, 3, 7 days, the nature of acute headache (dull pain, distending pain) was relieved more significantly, the number of patients with whole head headache was decreased more obviously in observation group [dull pain (cases): 16, 8, 3 vs. 28, 24, 18, distending pain (cases): 11, 6, 2 vs. 22, 16, 10, whole head pain (cases): 12, 5, 3 vs. 26, 20, 16, allP < 0.05]. With the prolongation of treatment, the VAS scores in the two groups were gradually decreased, on 7 days after treatment they reached to the lowest levels, and the degree of descent in the observation group was more significant than that in the control group (0.5±0.4 vs. 1.4±0.9,P < 0.05); thelevels of serum BNDF in the two groups were gradually increased after the 1st day of treatment, reached to the highest level on 7 days after treatment,and the degree of increase in observation group was more obvious than that in the control group (ng/L: 24.8±2.3 vs. 17.8±2.2). The therapeutic effective rate of the observation group was significantly higher than that of the control group [70.8% (68/96) vs. 53.3% (48/90),P < 0.05].Conclusion The combination of benzene sulfonic amlodipine and Yangxueqingnao granules can effectively relieve the acute headache in HU patients, and its mechanism is related to the increase in expression of BDNF.